Powrie J K, Smith G D, Hennessy T R, Shojaee-Moradie F, Kelly J M, Sönksen P H, Jones R H
Department of Endocrinology and Chemical Pathology, United Medical School, Guy's Hospital, London, UK.
Eur J Clin Invest. 1992 Apr;22(4):244-53. doi: 10.1111/j.1365-2362.1992.tb01458.x.
We have minimized methodological errors in the isotope dilution technique by using stable isotope, [6,6-2H2]glucose, thus avoiding the problem of contamination of tritiated glucose tracers and, by maintaining a constant plasma tracer enrichment have reduced error due to mixing transients. Using these modifications we have calculated hepatic glucose production in 20 patients with non-insulin-dependent diabetes mellitus during low (1 mU kg-1 min-1) and high (8 mU kg-1 min-1) dose insulin infusions. Mean fasting hepatic glucose production was 14.2 +/- 0.8 mumol kg-1 min-1. This suppressed by only 68% to 4.6 +/- 0.8 mumol kg-1 min-1 during the low-dose insulin infusion (plasma insulin 0.85 +/- 0.05 nmol l-1) and did not suppress further during the high-dose insulin infusion (plasma insulin 14.55 +/- 0.83 nmol l-1). Hepatic glucose production was significantly higher than zero throughout the study. Thus, we have found that minimization of known errors in the isotope dilution technique results in physiologically plausible and significantly positive values for hepatic glucose production indicating that the liver is resistant to insulin in patients with non-insulin-dependent diabetes mellitus.
我们通过使用稳定同位素[6,6 - 2H2]葡萄糖，将同位素稀释技术中的方法学误差降至最低，从而避免了氚标记葡萄糖示踪剂的污染问题。并且，通过维持血浆示踪剂富集度恒定，减少了混合瞬变引起的误差。采用这些改进方法，我们计算了20例非胰岛素依赖型糖尿病患者在低剂量（1 mU kg-1 min-1）和高剂量（8 mU kg-1 min-1）胰岛素输注期间的肝脏葡萄糖生成量。空腹时肝脏葡萄糖生成的平均值为14.2±0.8 μmol kg-1 min-1。在低剂量胰岛素输注期间（血浆胰岛素0.85±0.05 nmol l-1），该值仅被抑制68%，降至4.6±0.8 μmol kg-1 min-1，而在高剂量胰岛素输注期间（血浆胰岛素14.55±0.83 nmol l-1）并未进一步被抑制。在整个研究过程中，肝脏葡萄糖生成量均显著高于零。因此，我们发现，将同位素稀释技术中已知误差降至最低后，可得出符合生理且肝脏葡萄糖生成量显著为正的值，这表明非胰岛素依赖型糖尿病患者的肝脏对胰岛素具有抵抗性。
